Screening methods for identifying modulators of proliferation and differentiation of bone cells

Abstract

The present application relates to a compositions comprising a compound which modulates the activity of T1-M protein, the use of compounds which modulate the activity of T1-M protein, and an in vitro method for influencing the proliferation and/or differentiation potential of bone cells.

What is claimed is:  
     
       1. A method of assessing whether a composition is useful for modulating at least one of bone cell proliferation and bone cell differentiation, the method comprising comparing 
       a) expression of T1-M protein by a test cell maintained in the presence of the composition; and  
       b) expression of T1-M protein by a test cell maintained in the absence of the composition,  
       whereby a difference in expression of T1-M protein between the test cells is an indication that the composition is useful for modulating at least one of bone cell proliferation and bone cell differentiation. 
     
     
       2. The method of  claim 1 , wherein the composition comprises a compound that binds specifically with a T1 mRNA or its complement. 
     
     
       3. The method of  claim 2 , wherein the compound is a nucleic acid. 
     
     
       4. The method of  claim 3 , wherein the nucleic acid is selected from the group consisting of a T1-S antisense nucleic acid and a T1-M antisense nucleic acid. 
     
     
       5. The method of  claim 1 , wherein the test cells are K12 cells. 
     
     
       6. The method of  claim 1 , wherein the test cells are manipulated to express constitutively enhanced or reduced amounts of T1. 
     
     
       7. A method of assessing whether a composition is useful for enhancing bone cell proliferation, the method comprising comparing proliferation of test cells which comprise an exogenous expression vector encoding T1 protein and which express T1-M protein 
       a) in the presence of the composition and  
       b) in the absence of the composition,  
       whereby enhanced proliferation of the test cells in the presence of the composition, relative to proliferation of the test cells in the absence of the composition, is an indication that the composition is useful for enhancing bone cell proliferation. 
     
     
       8. The method of  claim 7 , wherein the test cells are K12 cells. 
     
     
       9. A method of assessing whether a composition is useful for enhancing bone cell differentiation, the method comprising comparing proliferation of test cells which comprise an exogenous expression vector encoding T1 protein and which express T1-M protein 
       a) in the presence of the composition and  
       b) in the absence of the composition,  
       whereby decreased proliferation of the test cells in the presence of the composition, relative to proliferation of the test cells in the absence of the composition, is an indication that the composition is useful for enhancing bone cell differentiation. 
     
     
       10. The method of  claim 9 , wherein the test cells are K12 cells.